The broad objective of the application is to develop immunologic reagents that will allow to interfere with the function of human P-Glycoprotein (P-170) that confers multi drug resistance on cancer cells, with the long term aim of producing favorable clinical therapeutical effects. The specific aims are: To produce new monoclonal antibodies against the human P-170, to test their efficacy to reverse multi drug resistance (MDR) in vitro and in an animal model, and to test their cytotoxic potential to MDR cells when coupled to toxins or in conjunction with Ca- channel blockers. To accomplish these aims, non-tumorigenic, immunogenic cell variants derived from a malignant mouse lymphoma will be used. These immunogenic variants and their parental tumorigenic lymphoma cells will be infected with the human MDR gene. Upon expression of this gene in the recipient cells the immunogenic variants will be inoculated into syngeneic Balb/c hosts to produce monoclonal antibodies that will specifically recognize human P-170. Analysis of monoclonal antibodies will be through immunofluorescence and western blotting analysis. Antibodies will then be tested on the parental malignant lymphoma cells infected with the MDR gene as to their ability to reverse MDR in vitro and in an animal model (syngeneic hosts and nude mice), thereby increasing the sensitivity of the malignant cells to anti-cancer drugs like Doxorubicin (Adriamycin).